Delving into the Latest Updates on BI-2536 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

PLK1

Action

inhibitors

Mechanism

PLK1 inhibitors(Polo like kinase 1 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication

Recurrent Aggressive Non-Hodgkin LymphomaAdvanced Malignant Solid Neoplasm

Inactive Indication

Metastatic castration-resistant prostate cancermetastatic non-small cell lung cancerNon-Small Cell Lung Cancer+ [5]

Originator Organization

C.H. Boehringer Sohn AG & Co. KG

Active Organization

Boehringer Ingelheim GmbH

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC28H39N7O3

InChIKeyXQVVPGYIWAGRNI-JOCHJYFZSA-N

CAS Registry755038-02-9

Determination of the maximum tolerated dose (MTD), safety, and tolerability when BI 2536 was given on Day 1 and Day 15 in combination with gemcitabine given on Day 1, Day 8 and Day 15 every 28 days in patients with locally advanced or metastatic pancreatic adenocarcinoma and characterisation the antitumor activity, pharmacokinetic (PK) profile, and CA 19-9 tumor marker response in response to the combination of BI 2536 with gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma.

Start Date01 Jun 2007

Sponsor / Collaborator

Boehringer Ingelheim GmbH

NCT00412880

/ CompletedPhase 2

An Open-label Phase II Trial to Investigate the Efficacy, Safety, and Pharmacokinetics of a Single Dose of 200 mg i.v. BI 2536 Administered Every 21 Days in Patients With Sensitive Relapse Small Cell Lung Cancer

Open label, uncontrolled Phase II trial to assess the efficacy and safety of BI 2536 in second line treatment in sensitive-relapse SCLC patients.

Start Date14 Feb 2007

Sponsor / Collaborator

Boehringer Ingelheim GmbH

100 Clinical Results associated with BI-2536

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100 Translational Medicine associated with BI-2536

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100 Patents (Medical) associated with BI-2536

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548

Literatures (Medical) associated with BI-2536

01 Mar 2025·Cancer Letters

Machine learning-based lactate-related genes signature predicts clinical outcomes and unveils novel therapeutic targets in esophageal squamous cell carcinoma

Article

Author: Jiao, Yunfei ; Xu, Yusi ; Bian, Yan ; Yu, Chuting ; Wang, Wei ; Gao, Ye ; Wang, Luowei ; Lin, Han ; Xin, Lei

Esophageal squamous cell carcinoma (ESCC), a predominant subtype of esophageal cancer, typically presents with poor prognosis. Lactate is a crucial metabolite in cancer and significantly impacts tumor biology. Here, we aimed to construct a lactate-related prognostic signature (LPS) for predicting prognosis in ESCC and uncovering potential therapeutic targets. We designed a computational framework to identify lactate-related genes (LRGs) and applied machine-learning to generate an optimal LPS model from 103 combinations. The LPS was evaluated for its predictive accuracy regarding patient prognosis, chemotherapy, radiotherapy, and immunotherapy. Analysis also covered genomic and proteomic traits linked to LPS-defined subtypes. The LPS model demonstrated robust and reliable accuracy in predicting survival outcomes in patients with ESCC. Patients with low LPS scores exhibited a more favorable prognosis and an enhanced response to both chemotherapy and radiotherapy. Conversely, patients with high LPS scores exhibited increased sensitivity to BI-2536 and panobinostat. Furthermore, a low LPS score was associated with better prognosis in multiple immunotherapy datasets across cancer types. Genetic amplifications and deletions were detected more frequently in the high-LPS than in the low-LPS group; however, no significant correlation was observed with the tumor mutation burden. Knockdown of GATM, a key LRG, significantly inhibited cell viability, proliferative capacity, and migration and invasion abilities in ESCC cell lines. In conclusion, the LPS score can be used to predict the prognosis of patients with ESCC and facilitate a more precise approach for selecting patients likely to respond to treatment.

01 Mar 2025·Nature Chemical Biology

A multiplex single-cell RNA-Seq pharmacotranscriptomics pipeline for drug discovery

Article

Author: Raivola, Juuli ; Piki, Emilia ; Ungureanu, Daniela ; Murumägi, Astrid ; Sharma, Subodh ; Dini, Alice ; Barker, Harlan

AbstractThe gene-regulatory dynamics governing drug responses in cancer are yet to be fully understood. Here, we report a pipeline capable of producing high-throughput pharmacotranscriptomic profiling through live-cell barcoding using antibody–oligonucleotide conjugates. This pipeline combines drug screening with 96-plex single-cell RNA sequencing. We show the potential of this approach by exploring the heterogeneous transcriptional landscape of primary high-grade serous ovarian cancer (HGSOC) cells after treatment with 45 drugs, with 13 distinct classes of mechanisms of action. A subset of phosphatidylinositol 3-OH kinase (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) inhibitors induced the activation of receptor tyrosine kinases, such as the epithelial growth factor receptor (EGFR), and this was mediated by the upregulation of caveolin 1 (CAV1). This drug resistance feedback loop could be mitigated by the synergistic action of agents targeting PI3K–AKT–mTOR and EGFR for HGSOC with CAV1 and EGFR expression. Using this workflow could enable the personalized testing of patient-derived tumor samples at single-cell resolution.

01 Mar 2025·Bioorganic & Medicinal Chemistry

Fine-tuning probes for fluorescence polarization binding assays of bivalent ligands against polo-like kinase 1 using full-length protein

Article

Author: Burke, Terrence R ; Tsuji, Kohei ; Tamamura, Hirokazu

Polo-like kinase 1 (Plk1) is an important cell cycle regulator that is a recognized target for development of anti-cancer therapeutics. Plk1 is composed of a catalytic kinase domain (KD), a flexible interdomain linker and a polo-box domain (PBD). Intramolecular protein-protein interactions (PPIs) between the PBD and KD result in "auto-inhibition" that is an essential component of proper Plk1 function. Recently, we developed high-affinity PBD-binding inhibitors using a bivalent approach. These ligands contain the low-nanomolar affinity Plk1 KD-binding inhibitors BI2536 or Wortmannin tethered to the PBD-binding peptide, PLH*SpT (H* represents a -(CH₂)₈Ph group on the histidine side chain π-nitrogen). Due to the extremely high affinity of these bivalent inhibitors, to avoid bottoming out in competitive binding assays, it was necessary to use PLH*SpT in the affinity probe. As reported herein, we have developed fluorescence polarization assays using a new fluorescent probe based on the Plk1 PBD-binding peptide, FDPPLHSpTA. We applied the assay to evaluate the affinities of bivalent inhibitors that possess a variety of PBD-binding peptides having much lower PBD-affinities than PLH*SpT. Tethering BI2536 in these bivalent inhibitors resulted in significant affinity enhancements as compared to the parent monovalent peptides.

100 Deals associated with BI-2536

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16107

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Recurrent Lung Small Cell Carcinoma	Phase 2	United States	Boehringer Ingelheim GmbH	14 Feb 2007
Recurrent Lung Small Cell Carcinoma	Phase 2	Canada	Boehringer Ingelheim GmbH	14 Feb 2007
Small Cell Carcinoma	Phase 2	Canada	Boehringer Ingelheim GmbH	14 Feb 2007
Small Cell Carcinoma	Phase 2	United States	Boehringer Ingelheim GmbH	14 Feb 2007
Relapsing acute myeloid leukemia	Phase 2	Austria	Boehringer Ingelheim GmbH	01 Oct 2006
Relapsing acute myeloid leukemia	Phase 2	Germany	Boehringer Ingelheim GmbH	01 Oct 2006
Metastatic castration-resistant prostate cancer	Phase 2	United Kingdom	Boehringer Ingelheim GmbH	01 Sep 2006
Pancreatic carcinoma non-resectable	Phase 2	Germany	Boehringer Ingelheim GmbH	01 Aug 2006
Pancreatic carcinoma non-resectable	Phase 2	Austria	Boehringer Ingelheim GmbH	01 Aug 2006
metastatic non-small cell lung cancer	Phase 2	Germany	Boehringer Ingelheim GmbH	25 Jul 2006

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00412880 (CTgov)	Phase 2	Recurrent Lung Small Cell Carcinoma \| Small Cell Carcinoma	23	BI 2536	(owwfawfvzo) = lsjzifqjhd ltcripsnqx (wkhvucgrnt, fjflyipxuc - fraufsqqah) View more	-	31 May 2022
NCT00376623 (CTgov)	Phase 2	metastatic non-small cell lung cancer	96	BI 2536 (200 Milligram (mg) BI 2536 (Day 1))	ffhremjdrw(zpkvhtoxqp) = vofiusaquy blyiqelupg (cgybkbnvsk, gqurikdvmu - vsawfbjgpi) View more	-	06 May 2022
NCT00376623 (CTgov)	Phase 2	metastatic non-small cell lung cancer	96	BI 2536 (50 Milligram BI 2536 (Day 1 - Day 3))	ffhremjdrw(zpkvhtoxqp) = pvbcqvrnrg blyiqelupg (cgybkbnvsk, xhjaemsufw - husoxlpcgg) View more	-	06 May 2022
NCT00710710 (CTgov)	Phase 2	Pancreatic carcinoma non-resectable	89	BI 2536 (200mg BI 2536 IV on Day 1)	(vclvfrblss) = hbezzgnspj tikgbtdlrq (veeosylwmp, xkwfykpmqe - uiiaocqlxh) View more	-	04 May 2022
NCT00710710 (CTgov)	Phase 2	Pancreatic carcinoma non-resectable	89	BI 2536 (60mg BI 2536 IV on Day 1-3)	(vclvfrblss) = bhwsfbdacd tikgbtdlrq (veeosylwmp, ptflburnke - edoqbyttyu) View more	-	04 May 2022
NCT00412880 (Pubmed \| Lung Cancer) Manual	Phase 2	Recurrent Lung Small Cell Carcinoma	23	BI 2536	(oanaogojqu) = bavqzdxuwn bcszswvhfv (utlpxxjukn ) View more	Negative	01 Feb 2017
ASCO2009	Phase 2	Recurrent Lung Small Cell Carcinoma	23	BI 2536	ifbtxyzpqn(mcpsmvobht) = yugjseyqkn uoiqjdbazr (jeisoexajk )	Negative	20 May 2009
ASCO2008	Phase 1	metastatic non-small cell lung cancer	33	BI 2536	(rdyibszegy) = guarhhgmxo ctpgxikdig (ksbqwklyke )	-	20 May 2008
ASCO2008	Phase 2	Metastatic castration-resistant prostate cancer	20	BI 2536 200 mg	(woxqqtkgla) = Grade 3/4 neutropenia was observed in 20%, and after escalation to 250 mg, in 73% of pts ghbmlpmczy (anmzfjckys ) View more	-	20 May 2008
ASCO2008	Phase 2	Recurrent Lung Small Cell Carcinoma	95	BI 2536 on Day 1	(goryslmnni) = hbbegozbbe geiytqayeb (tnvqkxddbq, 176–304) View more	-	20 May 2008
ASCO2006	Phase 1	Advanced Malignant Solid Neoplasm	42	BI 2536	(abuhlfsptp) = amekjtdywb ibeogeenqf (dephpaxzzk ) View more	-	20 Jun 2006
ASCO2006	Phase 1	HR-positive/HER2-low Solid Tumors	52	BI 2536	(yqxicmzjrv) = neutropenic infection artcmzkwyk (xlyyvegpbl )	-	20 Jun 2006